TY  - JOUR
UR  - http://dx.doi.org/10.1681/asn.0000000000000292
Y1  - 2024/03//
PB  - American Society of Nephrology
N2  - BACKGROUND: Metabolic acidosis is common in chronic kidney disease (CKD), but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. METHODS: In a Phase 3, double-blind, placebo-controlled trial, patients with CKD (estimated glomerular filtration rate [eGFR] of 20-40 mL/min/1.73 m2) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite endpoint of CKD progression, defined as the development of end-stage kidney disease (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of >40% from baseline, or death due to kidney failure. RESULTS: The mean (ąSD) baseline eGFR was 29.2 ą 6.3 mL/min/1.73 m2 and serum bicarbonate was 17.5ą1.4 mEq/L; this increased to 23.4 ą 2.0 mEq/L after the active-treatment run-in. Following randomized withdrawal, the mean serum bicarbonate was 22.0 ą 3.0 mEq/L and 20.9 ą 3.3 mEq/L in the veverimer and placebo groups at Month 3 and this ? 1mEq/L difference remained stable for the first 24 months. A primary endpoint event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95 % CI, 0.8 to 1.2; P=0.90). Serious and overall adverse event incidence did not differ between the groups. CONCLUSIONS: Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. (Funded by Tricida, Inc.; VALOR-CKD ClinicalTrials.gov number, NCT037102).
TI  - VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of Chronic Kidney Disease in Patients with Metabolic Acidosis
JF  - Journal of the American Society of Nephrology
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
VL  - 35
ID  - discovery10186395
AV  - public
A1  - Tangri, Navdeep
A1  - Mathur, Vandana S
A1  - Bushinsky, David A
A1  - Klaerner, Gerrit
A1  - Li, Elizabeth
A1  - Parsell, Dawn
A1  - Stasiv, Yuri
A1  - Walker, Michael
A1  - Wesson, Donald E
A1  - Wheeler, David C
A1  - Perkovic, Vlado
A1  - Inker, Lesley A
SP  - 311
EP  - 320
IS  - 3
ER  -